БНЗТ-2019

Boron nanoparticles as a potential target drug for boron neutron capture therapy

Not scheduled

15m

Academpark

Speaker

Ms Polina Khaptakhanova (Anatolievna)

Description

Boron neutron capture therapy (BNCT) is a binary anticancer technology realized through selective boron-10 isotope (10B) accumulation in tumor cells and further irradiation of the tumor area with epithermal neutrons. The neutron capture reaction results in decay of 10B atoms with the release of alpha-particles (bearing energy of 2.31MeV) producing double-strand breaks in tumor cell DNA. Along with the quality of a neutron source, the amount of 10B delivered to tumor cells is crucial for effective BNCT. Introduced decades ago, BNCT showed promising results in treatment of such diseases as head and neck cancer, malignant melanoma, and glioblastoma, though complete efficacy remains an elusive target. The most challenging remaining issue is the development of boron delivery agents that contain a large number of 10B atoms for achieving therapeutic concentrations in tumor cells (20-35 μg/g of tumor tissue, corresponding to ~ 10 billion 10B atoms per cell). Up to now, clinically used boron compounds for BNCT contained 1 (boron phenylalanine, or BPA) or 12 (sodium borocaptate, or BSH) 10B atoms per molecule [1-2]. We propose using boron nanoparticles as agents for BNCT that could significantly increase the number of 10B atoms delivered to tumor cells. With a 3 nm nanoparticle it is possible to deliver ~ 120 thousand 10B atoms, and about 2 million with a particle of 50 nm in diameter. We propose a new method for boron nanoparticles synthesis by cascade ultrasonic dispersion / destruction of elemental boron microparticles (10-20 µm) in an aqueous solution [3]. As the final form of the compound is presented as an aqueous particle dispersion, using water as a dispersion medium in our case is one of the main advantages over traditional methods of nanoparticles synthesis where product is obtained in the form of powder. In our method, ultrasonic dispersion provides degradation of large boron crystallites and formation of nanoscale particles less than 100 nm in diameter. The synthesized nanoparticles have been studied using dynamic light scattering, transmission electron microscopy, and X-ray crystallography. Cytotoxicity data showed boron concentrations, eligible for further irradiation experiments. The study is ongoing, and more detailed description will be provided at the conference. This work was supported by Russian Science Foundation (grant №19-72-30005). [1] A. Zelenetskii, S. Uspenskii [et al.]. Polycomplexes of Hyaluronic Acid and Borates in a Solid State and Solution: Synthesis, Characterization and Perspectives of Application in Boron Neutron Capture Therapy. Polymers 2018, 10, 181. [2] S. Uspenskii A. Zaboronok, T. Yamamoto, K. Nakai, F. Yoshida, M. Selyanin, A. Zelenetskii, A. Matsumura // Hyaluronic acid as a potential boron carrier for BNCT: Preliminary evaluation, 2015. Applied Radiation and Isotopes. V. 106. 181-184 pp. [3] S. Uspenskii, P. Khaptakhanova [et al.]. A method of obtaining a composition for boron neutron capture therapy of malignant tumors (options), RU, patent application №2019117707.